(S)-3-(4-(difluoromethoxy)phenyl)-5-(2-methoxy-2-phenylethoxy)-[1,2,4]triazolo[4,3-a]pyrazine

[alintheopen]

Synthesised in response to the OSM Christmas Wish List: http://malaria.ourexperiment.org/uri/791 Compound (S)-G - to test a single enantiomer of the alpha methoxy compound.

InChI=1S/C21H18F2N4O3/c1-28-17(14-5-3-2-4-6-14)13-29-19-12-24-11-18-25-26-20(27(18)19)15-7-9-16(10-8-15)30-21(22)23/h2-12,17,21H,13H2,1H3

FC(F)OC(C=C1)=CC=C1C2=NN=C3N2C(OCC@HOC)=CN=C3

[sdebbert]

I'm setting up our big undergrad-class-synthesis project in a few months -- I'm going to shoot for ethers like the one above, but probably with secondary alcohols instead of ethers. Should I stick to only single enantiomer alcohols (both R and S?) or just make the racemates?

For single enantiomer alcohols, I'd have them: first week: set up mandelic acid reduction, reflux 2 h second week: work up reduction, set up hydrazone formation from chlorohydrazinopyrazine (which has been synthesized by my TA's, themselves undergrads) third week: work up, set up cyclization with PIDA fourth: work up, set up nucleophilic substitution with (chiral) phenylethanediol synthesized earlier fifth: work up, column chromatography on final product

I'd like to try to make the simple phenylhydrazine derivative, as well as some of the non-aromatic-hydrazine lipophilic targets from the Wish List (and similar structures). Most of these reactions seem to be amenable to either short reflux times or letting them sit at rt for a long time, so I'm optimistic they'll translate to the classroom-lab nicely.

Any guidance as far as target selection is welcome!

[mattodd]

Sounds great Stefan.

Racemates would be fine, I think - we need to know they're active before we worry too much about enantiopure.

The simple phenylhydrazine derivative is compound T in http://malaria.ourexperiment.org/the_osm_blog/11379 right? And yes, those non-aromatic derivs are very interesting and definitely needed. What you say seems very reasonable in terms of time needed for the different bits. Much of the chemistry is now summarised on the wiki

http://openwetware.org/wiki/OpenSourceMalaria:Triazolopyrazine_%28TP%29_Series#Synthetic_Chemistry

I guess the unknown is the ease of hydrazone synthesis with non-Ar aldehydes.

On 7 March 2015 at 04:52, Stefan Debbert notifications@github.com wrote:

I'm setting up our big undergrad-class-synthesis project in a few months -- I'm going to shoot for ethers like the one above, but probably with secondary alcohols instead of ethers. Should I stick to only single enantiomer alcohols (both R and S?) or just make the racemates?

For single enantiomer alcohols, I'd have them: first week: set up mandelic acid reduction, reflux 2 h second week: work up reduction, set up hydrazone formation from chlorohydrazinopyrazine (which has been synthesized by my TA's, themselves undergrads) third week: work up, set up cyclization with PIDA fourth: work up, set up nucleophilic substitution with (chiral) phenylethanediol synthesized earlier fifth: work up, column chromatography on final product

I'd like to try to make the simple phenylhydrazine derivative, as well as some of the non-aromatic-hydrazine lipophilic targets from the Wish List (and similar structures). Most of these reactions seem to be amenable to either short reflux times or letting them sit at rt for a long time, so I'm optimistic they'll translate to the classroom-lab nicely.

Any guidance as far as target selection is welcome!

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